Clinical utility of plasma ctDNA sequencing in metastatic urothelial cancer

Clara Helal; Cédric Pobel; Arnaud Bayle; Damien Vasseur; Claudio Nicotra; Félix Blanc-Durand; Natacha Naoun; Alice Bernard-Tessier; Anna Patrikidou; Emeline Colomba; Ronan Flippot; Alina Fuerea; Nathalie Auger; Maud Ngo Camus; Benjamin Besse; Ludovic Lacroix; Etienne Rouleau; Santiago Ponce; Antoine Italiano; Yohann Loriot

doi:10.1016/j.ejca.2023.113368

Clinical utility of plasma ctDNA sequencing in metastatic urothelial cancer

Eur J Cancer. 2023 Dec:195:113368. doi: 10.1016/j.ejca.2023.113368. Epub 2023 Oct 6.

Authors

Clara Helal¹, Cédric Pobel², Arnaud Bayle³, Damien Vasseur⁴, Claudio Nicotra⁵, Félix Blanc-Durand⁵, Natacha Naoun⁶, Alice Bernard-Tessier⁷, Anna Patrikidou⁶, Emeline Colomba⁶, Ronan Flippot⁶, Alina Fuerea⁶, Nathalie Auger⁶, Maud Ngo Camus⁵, Benjamin Besse⁶, Ludovic Lacroix⁶, Etienne Rouleau⁶, Santiago Ponce⁵, Antoine Italiano⁵, Yohann Loriot⁸

Affiliations

¹ Sorbonne University, Paris, France; Département de médecine oncologique, Gustave Roussy, université Paris-Saclay, Villejuif, France.
² INSERM U981, Gustave Roussy, Villejuif, France.
³ INSERM U981, Gustave Roussy, Villejuif, France; Drug Development Department (DITEP), Gustave Roussy, Université Paris-Saclay, Villejuif, France.
⁴ Department of Pathology and Laboratory Medicine, Translational Research Laboratory and Biobank, Gustave Roussy, Université Paris-Saclay, Villejuif, France; AMMICA, INSERM US23/CNRS UMS3655,Gustave Roussy, Université Paris-Saclay, Villejuif, France.
⁵ Drug Development Department (DITEP), Gustave Roussy, Université Paris-Saclay, Villejuif, France.
⁶ Département de médecine oncologique, Gustave Roussy, université Paris-Saclay, Villejuif, France.
⁷ Département de médecine oncologique, Gustave Roussy, université Paris-Saclay, Villejuif, France; Drug Development Department (DITEP), Gustave Roussy, Université Paris-Saclay, Villejuif, France.
⁸ Département de médecine oncologique, Gustave Roussy, université Paris-Saclay, Villejuif, France; INSERM U981, Gustave Roussy, Villejuif, France; Drug Development Department (DITEP), Gustave Roussy, Université Paris-Saclay, Villejuif, France. Electronic address: Yohann.loriot@gustaveroussy.fr.

PMID: 37897866
DOI: 10.1016/j.ejca.2023.113368

Abstract

Background: Genomic stratification may help improve the management of patients with metastatic urothelial cancer (mUC), given the recent identification of targetable alterations. However, the collection of tissue samples remains challenging. Here, we assessed the clinical utility of plasma circulating tumour DNA (ctDNA) sequencing in these patients.

Methods: Patients with mUC were prospectively enroled in the STING trial (NCT04932525), in which ctDNA was profiled using the Foundation One Liquid CDx Assay (324 genes, blood tumour mutational burden [bTMB], microsatellite instability status). Each genomic report was reviewed by a multidisciplinary tumor board (MTB).

Results: Between January 2021 and June 2022, 140 mUC patients underwent molecular profiling. The median time to obtain the assay results was 20 days ((confidence interval) CI95%: [20,21]). The ctDNA analysis reproduced the somatic genomic landscape of previous tissue-based cohorts. Concordance for serial ctDNA samples was strong (r = 0.843 CI95%: [0.631-0.938], p < 0.001). At least one actionable target was detected in 63 patients (45%) with a total of 35 actionable alterations, including bTMB high (≥10 mutations/Mb) (N = 39, 21.1%), FGFR3 (N = 20, 10.8%), and Homologous recombination deﬁciency (HRD) alterations (N = 14, 7.6%). MTB recommended matched therapy in 63 patients (45.0%). Eight patients (5.7%) were treated, with an overall response rate of 50% (CI95%: 15.70-84.30) and a median progression-free survival (PFS) of 5.2 months (CI95%: 4.1 - NR). FGFR3 alterations were associated with a shorter PFS in patients treated with immunotherapy.

Conclusion: Overall, we demonstrated that genomic profiling with ctDNAs in mUC is a reliable and feasible approach for the timely initiation of genotype-matched therapies.

Keywords: Cell-free nucleic acids; Genomics; Immunotherapy; Liquid biopsy; Molecular targeted therapy; Precision medicine; Transitional cell carcinoma; Tumour biomarkers; Urinary bladder neoplasms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Circulating Tumor DNA* / genetics
Genomics / methods
High-Throughput Nucleotide Sequencing / methods
Humans
Mutation
Neoplasms*

Substances

Circulating Tumor DNA
Biomarkers, Tumor

Associated data

ClinicalTrials.gov/NCT04932525
ClinicalTrials.gov/NCT04932525